Hypertension or high blood pressure is one of the major health care problems in the United States and most developed countries. Traditionally, most studies done on the etiology of hypertension have focused on the arterial side of the circulation because of their predominant role as resistance vessels. While arterial resistance is definitely an important factor modulating blood pressure, an increased venous return to the heart due to venoconstriction could also affect blood pressure homeostasis. The overall hypothesis for this proposal is that the increased venomotor tone in the deoxycorticosterone acetate (DOCA)-salt model of hypertension is caused by an increased sensitivity of veins to sympathetic neural input and to the vasoconstrictor peptide endothelin (ET-1). By combining in-vitro (vasoconstriction measurements, transmural nerve stimulation), in-vivo (hemodynamic measurements in conscious animals) and molecular (Western blotting, immunohistochemistry) techniques we will try to elucidate the mechanisms responsible for the increased venomotor tone seen early in hypertension. Answers to these questions will provide a basic understanding of venous function that could lead to better pharmacological approaches not only for hypertension treatment but also for any disease in which there is a vein dysfunction. [unreadable] [unreadable]